Overcoming the Bioanalysis Challenges of Biosimilars:
Rituximab Case Study
As Biosimilar compounds are not exact duplicates of Innovator Biotherapeutics, the Regulatory Agency requirements differ from those of small molecules. One important difference is the required evaluation of "similarity" of the Biosimilar compared to the innovator Biologic compound.
Bioanalysis of Biosimilar compounds is subject to endogenous interference, requiring specific and selective assay to ensure data reliability. The specificity and selectivity of traditional quantification approaches (Ligand Binding Assays - LBA) are dependent on the interaction of critical reagents to the Biotherapeutic. It is possible that the Innovator and the Biosimilar do not have the same binding characteristics towards the assay critical reagents. In this case, two assays with different critical reagents may be needed and the demonstration of biocomparability may be more complicated.
LCMS and more recently HRMS have been gaining momentum as an important alternative for the Bioanalysis of Biotherapeutics. Unlike traditional approaches, LCMS assays can be developed for Biosimilar Bioanalysis without using critical reagents and therefore only a single LCMS assay is needed for both Biosimilar and Innovator comparison. Algorithme Pharma has recently demonstrated the applicability of this approach in a case study on the application of HRMS in the Quantification of Rituximab.